What is the biochemical basis of depression?
Imbalance in biogenic amine neurotransmitter systems
Neurochemical effects of tricyclic antidepressants
Blockade of transmitter uptake -- NE and 5-HT
What are the most commonly used anti-depressants? What are the two we need to know?
SSRIs --Fluoxetine and Sertraline
Common SE of SSRIs?
N/V, Insomnia, Nervousness, Sexual dysfunction
What is serotonin reaction and why can it occur?
In the presence of MAOI's Include hyperthermia, muscle rigidity and CV collapse
What is SSRI Discontinuation syndrome?
Occurs within 1 to 7 days after stopping an SSRI; Most common with shorter acting drugs like sertraline; Symptoms include: dizziness, light-headedness, vertigo, anxiety, fatigue, h/a, tremor, visual disturbances
Clinical uses of SSRI's:
MDD, OCD, Panic disorder, social phobia, PTSD, GAD, PMS
First SSRI on the market, Active metabolite with long half-life, Effects on drug metabolism
SSRI, Similar to fluoxetine with less effects on drug metabolism, shorter half-life
Blocks both serotonin and Norepinephrine uptake
SNRI, 12-18 hour half-life, Use with caution in patients with liver disease Approved for use with fibromyalgia, diabetic neuropathy, back pain, and osteoarthritis pain
Drugs without typical tricyclic structure or SSRI action; may or may not block catecholamine uptake
Atypical antidepressant; approved for nicotine withdrawal and seasonal disorder; blocks NE and dopamine uptake
Atypical antidepressant; blocks presynaptic alpha2 receptors in the brain; increases appetite
First highly effective drugs for the treatment of depression; now used secondarily to SSRI's and other newer cmpds
Pharmacological properties of tricyclic antidepressants
1. produces elevation of mood in depressed patients after 2-3 weeks 2. Decreases REM and increase stage 4 sleep 3. Prominent anticholinergic effects 4. Sedation 5. Cardiac abnormalities
Symptoms of overdose with TCA
hyperpyrexia, hyper/hypotension, seizures, coma, cardiac conduction defects
Drug interactions with TCA's
Guanethidine -- blocks guanethidine uptake Sypathomimetic drugs -- particularly indirect acting ones Effects on absorption and metabolism of other drugs
Therapeutic uses of TCA's
MDD, Enuresis in childhood; chronic pain (amitriptyline); OCD (Clomipramine)
Two TCA's we need to know and what they're used for
Amitriptyline --> chronic pain Clomipramine --> OCD
Block the oxidative deamination of naturally occurring biogenic amines like NE, DA and 5-HT and ingested amines
Irreversible inhibitor of MAO
What do you have to watch in your diet if you're on MAOI's?
Major mental disorder characterized by derangement of personality and loss of contact with reality, delusions, hallucinations
Which dopamine receptor activates adenylyl cyclase?
Which dopamine receptor inhibits adenylyl cyclase?
Which two receptors do atypical antipsychotic drugs act on?
DA + 5HT2 receptors
Actions of typical antipsychotic drugs
Decrease psychotic behavior, sedation, extrapyramidal actions, neuroendocrine effects, orthostatic hypotension; weight gain; neuroleptic malignant syndrome
Prototype available typical antipsychotic drugs (Class)
Phenothiazines-- 3 subtypes based on side chain: Chlorpromazine, Thioridazine, Fluphenazine
Compounds with aliphatic side chains; low to medium potency, sedative, pronounced anticholinergic actions
Compounds with piperidine side chains; low potency, sedative, less extrapyramidal actions, anticholinergic
Compounds with piperazine side chains; high potency, less sedative, less anticholinergic, more extrapyramidal reactions
Butyrophenone Derivative, not chemically related to phenothiazines but pharmacologically similar to high potency piperzine derivatives
Clozapine, Olanzapine, Risperidone, Quetiapine, Aripiprazole
Less extrapyramidal symptoms, May cause serious agranulocytosis, weight gain; Effects on negative symptoms
More potent 5-HT2 antagonist; few extra pyramidal symptoms; no agranulocytosis; weight gain and diabetes risk
Combined dopamine and serotonin receptor antagonist; low incidence of extrapyramidal side effects
Structurally related to clozapine with effects on D2 and 5-HT2 receptors; some abuse potential
D2 partial agonist -- approved as an adjunct in the treatment of depression
Uses of atypical antipsychotics
Acute psychotic episodes, chronic schizo, manic episodes, augmentation of antidepressant action, Tourette's, Antiemesis